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Dr Chong Shu Ling - Paediatric head injury

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Dr Chong Shu Ling delivers a tour de force on traumatic head injuries in childrem

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Dr Chong Shu Ling - Paediatric head injury

  1. 1. PEDIATRIC HEAD INJURY Dr Chong Shu-Ling Department of Emergency Medicine
  2. 2. Objectives Which head-injured child requires a CT scan? Hyperosmolar agents Analgesics, Sedatives and Neuromuscular blockers Hyperventilation Prophylactic Anti-epileptics Glycemic Control Cooling heads in pediatric TBI
  3. 3. You are on shift when… A 7-year-old girl is brought into your Emergency Department by paramedics with her head bandaged. According to the paramedics, she was crossing the road when she was hit by an oncoming taxi. She was flung about 2 meters.
  4. 4. Case Scenario cont’d According to the paramedics, the 7-year-old girl was crossing the road when she was hit by an oncoming taxi. She was flung about 2 meters. On physical examination, she is crying softly, but is able to tell you her name, and lifts her right hand when asked to. Vital signs: HR 140/min, RR 30/min BP 100/60mmHg SaO2 96% on room air. Pupils are 3mm equal and reactive bilaterally Kept on hard cervical collar
  5. 5. According to the paramedics, the 7-year-old girl was crossing the road when she was hit by an oncoming taxi. She was flung about 2 meters. On physical examination, she is crying softly, but is able to tell you her name, and lifts her right hand when asked to. Vital signs: HR 140/min, RR 30/min BP 100/60mmHg SaO2 96% on room air. Pupils are 3mm equal and reactive bilaterally Kept on hard cervical collar After removing her bandage – you notice a boggy swelling over the right parietal region. There is no active bleeding currently.
  6. 6. After you log roll, she complains of headache and vomits once. She suddenly appears disoriented and seems very agitated. Which of the following clinical features is the greatest indication for a CT brain? A) Headache B) Vomiting once C) New onset agitation D) Dangerous mechanism of injury E) Presence of scalp hematoma
  7. 7. Before answering the question..
  8. 8. Is CT scan dangerous? • Lethal malignancies occur between 1-in-1000 and 1-in-5000 paediatric cranial CT scans • Risk increases with decreasing age • ALARA Brenner DJ. Estimating cancer risks from pediatric CT: going from the qualitative to the quantitative. Pediatr Radiol 2002 Brenner DJ, Hall EJ. Computed tomography – An increasing source of radiation exposure. N Engl J Med 2007 Shah NB, Platt SL. ALARA: Is there a cause for alarm? Reducing radiation risks from computed tomography scanning in children. Curr Opin Pediatr 2008
  9. 9. Is CT scan dangerous? • Cancer risk in 680, 000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians • Matthews JD et al. BMJ 2013; 346:f2360 • Cancer incidence was 24% greater for exposed than for unexposed people, after accounting for age, sex and year of birth. • Incidence Rate Ratio (IRR) increased significantly for many types of solid cancers, leukemia or myelodysplasia For brain cancer and all cancers combined – IRR was greater at younger ages
  10. 10. Is CT scan dangerous? •CT of the brain was significantly associated with the risk of brain tumours (as was CT to the red bone marrow, with the risk of leukaemia) • MS Pearce et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 2012;380:499-505
  11. 11. 1999 Royal College of Surgeons of England 2001 Canadian CT head rule Stiell IG. Lancet 2001 National Collaborative Centre for Acute Care. Published by NICE guidelines Implications of NICE guidelines on management of children presenting with head injury J Dunning Arch Dis Child 2004 CHALICE Clinical Prediction Rule J Dunning. Arch Dis Child 2006 PECARN rule Kupperman. Lancet 2009 2003 2006 2009 CATCH rule Osmond. CMAJ 2010 Should a head-injured child receive a head CT scan? A systemic review of clinical prediction rules. Macguire JL. Pediatrics 2009 Comparing CATCH, CHALICE and PECARN. Lyttle. Emerg Med J Jan 2012 2009 2010
  12. 12. CHALICE Children’s Head injury Algorithm for the prediction of Important Clinical Events J Dunning et al. Arch Dis Child 2006;91:885-91 • Prospective Cohort study from 2000-2003 (n=22772) • Outcome measure: composite comprising death, neurosurgical intervention, or marked abnormalities on CT • Safer than Canadian CT head rule • May increase rate of CT scanning History -Witnessed LOC > 5 mins -History of amnesia (either antegrade or retrograde) > 5 mins -Abnormal drowsiness -≥ 3 vomits after HI -Suspicion on NAI -Seizure after HI Examination -GCS< 14, or < 15 if < 1 yr old -Suspicion of penetrating or deprassed skull fracture of tense fontanelle -Signs of basal skull fracture -≥Focal neurological deficit -Presence of bruise, swelling or laceration > 5 cm if < 1 yr old Mechanism -High-speed road traffic accident either as pedestrian, cyclist or occupant (speed >40m/h) -Fall of > 3m in height -High speed injury from a projectile or an object
  13. 13. 1999 Royal College of Surgeons of England 2001 Canadian CT head rule Stiell IG. Lancet 2001 National Collaborative Centre for Acute Care. Published by NICE guidelines Implications of NICE guidelines on management of children presenting with head injury J Dunning Arch Dis Child 2004 CHALICE Clinical Prediction Rule J Dunning. Arch Dis Child 2006 PECARN rule Kupperman. Lancet 2009 2003 2006 2009 CATCH rule Osmond. CMAJ 2010 Should a head-injured child receive a head CT scan? A systemic review of clinical prediction rules. Macguire JL. Pediatrics 2009 Comparing CATCH, CHALICE and PECARN. Lyttle. Emerg Med J Jan 2012 2009 2010
  14. 14. Identifying children with very low risk of CITBI • Large Prospective cohort study • N=42,412 for derivation and validation populations • Aim • To derive and validate a prediction rules for ciTBI • Sought to derive clinically important outcomes • Death, Neurosurgery, Intubation > 24 hrs, Hospitalization ≥ 2 days • To identify children at very low risk in whom CT heads may be unnecessary Kuppermann N.(PECARN) Lancet 2009; 374: 1160-1170
  15. 15. Children > 2 years GCS = 14 or other signs of altered mental status, or Signs of basilar skull fracture Yes 4.3% risk of ciTBI CT Recommended No History of LOC History of Vomiting Severe mechanism of injury Severe headache Yes 0.9% risk of ciTBI Observation vs CT: -Physician experience -Multiple vs isolated findings -Worsening symptoms and signs -Parental preference No CT Not Recommended Kuppermann N. Lancet 2009; 374: 1160-1170
  16. 16. Children < 2 years GCS = 14 or other signs of altered mental status, or Palpable skull fracture Yes 4.4% risk of ciTBI CT recommended No Occipital/Parietal/Temporal scalp hematoma History of LOC > 5s Severe mechanisms of injury Not acting normally as per parent Yes 0.9% risk of ciTBI Observation vs CT: -Physician experience -Multiple vs isolated finding -Worsening symptoms or signs -Age < 3 months -Parental preference No CT Not Recommended Kuppermann N. Lancet 2009; 374: 1160-1170
  17. 17. 1999 Royal College of Surgeons of England 2001 Canadian CT head rule Stiell IG. Lancet 2001 National Collaborative Centre for Acute Care. Published by NICE guidelines Implications of NICE guidelines on management of children presenting with head injury J Dunning Arch Dis Child 2004 CHALICE Clinical Prediction Rule J Dunning. Arch Dis Child 2006 PECARN rule Kupperman. Lancet 2009 2003 2006 2009 CATCH rule Osmond. CMAJ 2010 Should a head-injured child receive a head CT scan? A systemic review of clinical prediction rules. Macguire JL. Pediatrics 2009 Comparing CATCH, CHALICE and PECARN. Lyttle. Emerg Med J Jan 2012 2009 2010
  18. 18. CATCH Rule Osmond et al. (PERC) CMAJ 2010;182:341-8 • Prospectively derived Clinical Decision Rule Classified as no ciTBI if they were well on telephone follow up at 14 days • N= 3866 patients (277 < 2 yrs old) • 24 (0.6%) underwent a neurologic intervention • 159 (4.1%) had any brain injury as demonstrated on CT
  19. 19. CATCH Rule Osmond et al. (PERC) CMAJ 2010;182:341-8 CATCH RULE for Childhood Head Injury CT of the head is required if: HIGH RISK (need for neurologic intervention) 1. GCS < 15 - 2 hours after injury 2. Suspected open or depressed skull fracture 3. History of worsening headache 4. Irritability on examination MEDIUM risk (brain injury on CT scan) 5. Any sign of basal skull fracture 6. Large, boggy hematoma of scalp 7. Dangerous mechanism of injury -Sensitivity 100% -Specificity 70.2% -Require 30.2% to undergo CT -Sensitivity 98.1% -Specificity 50.1% -Require 51.9% to undergo CT
  20. 20. Which Clinical Decision Rule, rules? Comparing CATCH, CHALICE and PECARN clinical decision rules for paediatric head injuries Lyttle et al. Emerg Med J Feb 2012
  21. 21. Comparing Accuracy of Clinical Decision Rule Lyttle et al. Emerg Med J. Feb 2012 Sensitivity Specificity NPV PPV Need for Neurological intervention CATCH 100% 70.2% 100% 2.1% Clinically significant intracranial injury CHALICE 98.6% 86.9% 99.9% 8.6% Clinically significant intracranial injury in patients with GCS 13-15 CHALICE 97.6% 87.3% 99.9% 5.4% Clinically important brain injury PECARN < 2yrs 98.6% 53.7% 99.9% 1.8% PECARN ≥ 2yrs 96.7% 58.5% 99.9% 2.0% CT Visible brain injury CATCH 98.1% 50.1% 99.8% 7.8% CHALICE 98.6% - - - PECARN < 2yrs Not possible to calculate – derivation group reported only ciTBI PECARN ≥ 2yrs
  22. 22. Comparing Predictor Variables Lyttle et al. Emerg Med J. Feb 2012
  23. 23. Which Clinical Decision rule, rules? • PECARN rule was the only one prospectively validated • PECARN rule divided those < 2 yrs old from those ≥ 2 yrs old • Shift from identifying any lesion on CT to focusing on clinically significant lesions makes results difficult to compare • 3 CDRs need to undergo process of prospective validation and comparison in single population
  24. 24. Conclusion • Best Rule? • ROLE OF OBSERVATION • Nigrovic et al. (PECARN) Pediatrics June 2011 • The Effect of Observation on Cranial Computed Tomography Utilization for Children After Blunt Head Trauma • 42,412 patients in prospective multicentre observational study • If patients were observed before making a decision on CT, CT rate was lower (31% vs 35%)
  25. 25. What about us? •Retrospective data – N = 2380 (7 month retrospective series) – 537 patients admitted (22.6%) , 49 patients had a CT brain (2.1%), while only 15 patients (0.6%) had a significant finding on CT (bleed, edema or fracture). •Small prospective study on applicability of the CATCH, PECARN and CHALICE rules in our local population –N=77 (3 week period) –We applied the above rules to our population but found that they would increase the rate of CT in our centre from 2-3% to about 30%.
  26. 26. WHAT ABOUT US?
  27. 27. Back to the patient…. According to the paramedics, the 7-year-old girl was crossing the road when she was hit by an oncoming taxi. She was flung about 2 meters. Suddenly she turns drowsy. She opens her eyes only to pain. On applying nail bed pressure she adopts a flexing posture but is unable to withdraw her arm from the stimulus. She moans intermittently.
  28. 28. 1 2 3 4 5 6 Eyes Does not open eyes Opens to painful stimuli Opens to speech Opens spontaneously N/A N/A Verbal No verbal response Inconsolable, agitated Inconsistently inconsolable, moaning Cries but consolable, inapproriate interactions Smiles, interacts, follows objects N/A Motor No motor response Extension to pain (decerebrate response) Abnormal flexion to pain (decorticate response) Withdraws from pain Localizes painful stimuli Obeys commands GCS scoring in children
  29. 29. 1 2 3 4 5 6 Eyes Does not open eyes Opens to painful stimuli Opens to speech Opens spontaneously N/A N/A Verbal No verbal response Inconsolable, agitated Inconsistently inconsolable, moaning Cries but consolable, inapproriate interactions Smiles, interacts, follows objects N/A Motor No motor response Extension to pain (decerebrate response) Abnormal flexion to pain (decorticate response) Withdraws from pain Localizes painful stimuli Obeys commands GCS scoring in children
  30. 30. 1 2 3 4 5 6 Eyes Does not open eyes Opens to painful stimuli Opens to speech Opens spontaneously N/A N/A Verbal No verbal response Inconsolable, agitated Inconsistently inconsolable, moaning Cries but consolable, inapproriate interactions Smiles, interacts, follows objects N/A Motor No motor response Extension to pain (decerebrate response) Abnormal flexion to pain (decorticate response) Withdraws from pain Localizes painful stimuli Obeys commands GCS scoring in children
  31. 31. 1 2 3 4 5 6 Eyes Does not open eyes Opens to painful stimuli Opens to speech Opens spontaneously N/A N/A Verbal No verbal response Inconsolable, agitated Inconsistently inconsolable, moaning Cries but consolable, inapproriate interactions Smiles, interacts, follows objects N/A Motor No motor response Extension to pain (decerebrate response) Abnormal flexion to pain (decorticate response) Withdraws from pain Localizes painful stimuli Obeys commands GCS scoring in children
  32. 32. What should you do next? Vital signs: HR 138/min RR 30/min, BP 110/56 mmHg SaO2 100% on 100% NRM What should you do next? Preparing for RSI…….
  33. 33. Analgesics, sedatives and neuromuscular blockade • Facilitate ability to maintain airway, vascular catheters and other invasive interventions • Anti-convulsant and anti-emetic properties • Attenuate effects of pain and stress: • Increased cerebral metabolic demands that increase cerebral blood volume and raise ICP, increased metabolic rate with higher oxygen requirements • Raju et al. Intracranial pressure during intubation and anesthesia in infants. J Pediatr 1980;96:860-862 • NM-blockers prevent shivering, posturing and breathing against the ventilator • Hsiang JK et al.Early, routine paralysis for intracranial pressure control in severe head injuiry: is it necessary? Crit Care Med 1994;22:1471-1476 Analgesics, sedatives and NM blockers
  34. 34. Key Studies of Prospective trials of Ketamine and Intracranial Pressure CJEM 2010;12(2)154-7 Study Study Type Study Population ICP CPP Bourgoin 2003 Prospective double-blind RCT - 25 patients with severe head injury - continuous infusion ketamine-midazolam v sufentanil-midazolam infusion No significant difference between groups No significant difference between groups Bourgoin 2005 Prospective double-blind RCT - 30 patients with TBI receiving sufentanil-midazolam or ketamine-midazolam using target controlled infusion No significant difference between groups No significant difference between groups Schmittner 2007 Randomized prospective trial -24 patients with TBI -Group 1: methohexitone + ketamine sedation Group 2: methohexitone + fentanyl sedation No significant difference between groups No significant difference between groups Bourgoin et al. Crit care Med 2003;31:711-7 Bourgoin et al. Crit Care Med 2005;33:1109-13 Schmittner et al. J Neurosurg Anesthesiol 2007;19:257-62 Analgesics, sedatives and NM blockers
  35. 35. Key Studies of Prospective trials of Ketamine and Intracranial Pressure Reference Study Description Data Quality and Reasons Results and Conclusion Bar-Joseph et al 2009 Prospective series N = 30 children with raised ICP, 24 with non-penetrating TBI Protocol: Single dose of ketamine (1-1.5mg/kg) evaluated for ability to: (1) Prevent further increase in ICP during stressful procedures (2) Treat refractory intracranial hypertension No control for confounders, small sample size, admission GCS not specified, sample included pathologies other than severe TBI Ketamine reduced ICP for both settings Increase CPP Bar-Joseph G et al. Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension J Neurosurg Pediatr 2009;4:40-46 Analgesics, sedatives and NM blockers
  36. 36. After intubation Vital signs: HR 144/min, BP 100/50 mmHg SaO2 100% while bagging What should you do next? A) Hyperventilation B) Hyperosmolar agents C) Give anti-epileptic therapy
  37. 37. Hyperventilation • Reduces ICP by producing hypocapnia-induced cerebral vasoconstriction • Reduces cerebral blood flow (CBF) and cerebral blood volume • Studies in mixed adult and pediatric populations have demonstrated that hyperventilation results in decreased cerebral oxygenation and may induce brain ischemia • Kiening KL et al. Brain tissue pO2-monitoring in comatose patients: implication for therapy. Neurol Res 1997;19:233-240 • Schnieder GH et al. Continuous monitoring of jugular bulb oxygen saturation in comatose patients – Therapeutic implications. Acta Neurochir (Wien) 1995;134:71-75 Hyperventilation
  38. 38. Reference Study Description Data Quality and Reasons Results and Conclusion Skippen et al 1997 Case series N = 23 Mean age 11 yrs Protocol: CBF measured by xenon-enhanced CT during partial pressure of arterial CO2 adjusted to > 35, 25-35, and < 25mmHg Outcome: Ischemic threshold defined as < 18 ml/100g/min No control for confounders Areas of CBF below ischemic threshold 28.9%, 59.4% and 73.1% respectively Curry et al 2008 Retrospective cohort study N = 464 Mean age 8 yrs Outcome: incidence of severe hypocarbia (pCO2 < 30mmHg) during the initial 48 hours and risk of inpatient mortality Unclear if outcome assessment methods unbiased Severe hypocarbia 60% before and 52% after (p=0.19) Mortality adjusted odds ratio of 1.44 (For 1 episode), 4.18 (for 2 episodes) and 3.93 for 3 or more episodes of severe hypocarbia Pediatr Crit Care Med 2012 Vol 13 Hyperventilation
  39. 39. Hyperventilation • Avoid prophylactic severe hyperventilation to PaCO2 < 30mmHg in initial 48 hours after injury • If hyperventilation is used in management of refractory intracranial hypertension, advanced neuromonitoring for evaluation of cerebral ischemia should be considered
  40. 40. HYPEROSMOLAR AGENTS
  41. 41. Use of Hyperosmolar agents: Mannitol • Uses: Reduces blood viscosity and has osmotic effect (moving water from parenchyma into systemic circulation) • Osmotic effects last up to 6 hours and requires intact blood brain barrier (Bouma et al. J Neurotrauma 1992;9(Suppl 1): S333-348) • Mannitol may accumulate in injured brain regions, where reverse osmotic shift may occur with fluid moving from the intravascular compartment into the brain parenchyma – worsening raised ICP. • Kaieda R et al. Neurosurgery 1989;24:671-678 • Use of mannitol (excreted unchanged in the urine) may risk development of acute tubular necrosis and renal failure • The Brain Trauma Foundation. Use of Mannitol J Neurotrauma 2000;17:521-525 Hyperosmolar agents
  42. 42. Hyperosmolar agents: Hypertonic saline • Low penetration of blood-brain barrier, shares favorable osmolar gradient • Treats hyponatremia (can cause cell swelling and seizures) • Result of cerebral salt wasting, SIADH, Na losses from CSF drainage, iatrogenic causes • Pediatr Crit Care Med 2012 Vol 13, No. 1(Suppl.) • Side effects • Rebound in ICP, central pontine myelinolysis, renal impairment, natriuresis, masking of development of diabetes insipidus • Qureshi AI et al. Crit Care Med 2000;28:3301-3313 Hyperosmolar agents
  43. 43. Hypertonic Saline Reference Study Description Data Quality and Reasons Results and Conclusion Fisher et al 1992 Randomized controlled crossover trial N = 18 Mean age 8.3 yr Protocol: 3% saline vs 0.9% saline Randomization and allocation concealment methods not reported. Crossover study lacking reporting on first period comparison of baseline characteristics; small sample size During 2 hour trial, hypertonic saline was associated with lower ICP and reduced need for additional interventions to treat ICP Simma et al 1998 Randomized controlled trial N=35 Mean age 87 months Protocol: 1.7% hypertonic saline vs lactated Ringer’s administered for 3 days Not blinded, insufficient power No difference in survival rates Those with hypertonic saline required fewer interventions, had shorter length of ICU stay and shorter mechanical ventilation Fisher B et al. Hypertonic saline lowers raised intracranial pressure in children after head trauma. J Neurosurg Anesthesiol 1992;4:4-10 Simma B et al. A prospective, randomized and controlled study of fluid management in children with severe head injury: Lactated Ringer’s solution versus hypertonic saline. Crit Care Med 1998;26:1265-1270
  44. 44. Hypertonic Saline Reference Study Description Data Quality and Reasons Results and Conclusion Peterson et al 2000 Retrospective chart review N =68 Mean age 7.8 years Protocol : Use of continuous infusion of 3% hypertonic saline to reduce ICP Retrospective, no control for confounders Survival rate was higher than expected based on Trauma and Injury Severity Score None developed central pontine myelinolysis, SAH or rebound increase in ICP Khanna et al 2000 Prospective Observational Study N = 10 Protocol: Use of 3% hypertonic saline to maintain ICP < 20mmHg in children with raised ICP resistant to conventional therapy Small study Mean duration of treatment was 7.6 days Reduction in ICP spikes and increase in cerebral perfusion pressure were seen during treatment with 3% hypertonic saline Peterson B, et al. Prolonged hypernatremia controls elevated intracranial pressure in head-injured pediatric patients. Crit Care Med 2000;28:1136-1143 Khanna S et al. Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury. Crit Care Med 2000;28:1144-1151
  45. 45. After intubation, while waiting for transfer, you wonder about the use of phenytoin as a prophylactic anti-epileptic.
  46. 46. Post traumatic Seizures (PTS) • Early: Within 7 days of injury • Late: Beyond 8 days of injury • Risk factors for PTS include: Age, intraparenchymal hemorrhage, retained bone and metal fragments, depressed skull fracture, focal neurological deficits, LOC, GCS < 10, severity of injury, length of post-traumatic amnesia, subdural or epidural hematoma, penetrating injury. • Ates O et al. Post-traumatic early epilepsy in pediatric age group with emphasis on influential factors. Childs Nerv Syst 2006;22:279-284 • Appleton RE et al. Post-traumatic epilepsy in children requiring inpatient rehabilitation following head injury. J Neurol Neurosurg Psychiatry 2002;72:669-672
  47. 47. Post Traumatic Seizures • Infants and children have lower seizure thresholds • Holmes GL et al. Pediatr Neurol 2005;33:1-11 • Seizures may be subtle and challenging to diagnose in critically head injured children • Bratton SL et al. Guidelines for management of severe traumatic brain injury. XIII: Antiseizure prophylaxis. J Neurotrauma 2007;24 (Suppl 1): S83-S86 • Adult guidelines recommend use of anticonvulsants to decrease incidence of early PTS • Temkin NR et al. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med 1990;323:497-502 • Incidence of early PTS was 3.6% in the phenytoin group vs 14.2% in placebo group (RR 0.27 {95% CI 0.12-0.62} Anti-epileptic Therapy
  48. 48. Citation Study Group Study Type Outcome Key Results Comments Schierhout et al 2001 6 controlled trials, 1218 randomized (both) adults and children System -atic review Early seizures (first 7 days), late seizures, mortality, neurologic disability (GOS) RR for early seizure prevention 0.34 (CI0.21-0.54) NNT 10 No difference for death, neurologic disability and late seizures Early seizure prevention values represent 4 studies with phenytoin and 2 with other agents EA Hunt. Phenytoin in traumatic brain injury. Towards evidence based medicine for paediatricians. Arch Dis Child 2002;86:59-63 Anti-epileptic Therapy
  49. 49. Reference Study Description Data Quality and Reasons Results and Conclusion Lewis et al 1993 Retrospective cohort study N = 194 (31 with severe TBI) Median age 6 yrs Protocol: Phenytoin within 24 hours of hospital admission or no prophylactic anticonvulsant medication Outcome: Any seizure during hospitalization Control for confounders only in analysis of predictors of seizure, not for comparison of groups based on seizure prophylaxis Reduction in early PTS rate in severe TBI cases (GCS 3-8) treated with phenytoin (15% vs 53%) Young et al 2004 Randomized, double-blinded, placebo-controlled N = 103 Age range: < 16 yrs Protocol: Enrolled within 40 mins of presentation and drug or placebo administered within 60 mins. Limitations: Low seizure rate, small sample size from loss to follow up. 33% Lost at 48 hr follow up and 36% lost at 30 day follow up No reduction in rate of PTS within 48 hours of injury (7% in phenytoin group vs 5% in placebo group) Pediatr Crit Care Med 2012 Vol 13 Anti-epileptic Therapy
  50. 50. • The hypocount returns 15.6mmol/L What should you do now? A) Give subcutaneous insulin 0.1 units/kg B) Start IV insulin at 0.1units/kg/hour C) Repeat glucose in 2 hours
  51. 51. Study Design Inclusion criteria (total n) Results Comments JRT Melo et al [1], [2] Retrospective cross-sectional Children < 17 years old with severe TBI as defined by GCS ≤ 8 (n = 315) Hyperglycemia ≥11.1 mmol/L (≥200mg/dl) is an independent predictor for mortality – OR 6.14 (95% CI 2.25-16.73) A new scale was proposed – this included: age group, GCS, temperature, blood glucose levels and prothrombin time SM Seyed Saadat et al [3] Retrospective cross-sectional Children < 18 years old with severe TBI as defined by GCS ≤ 8, admitted to ED within 12 hours of injury (n=122) Persistent hyperglycemia during the first 2-3 days had adjusted ORs for mortality of 2.84 (95% CI 0.89-9.06) and 11.11 (95% CI 2.95-41.71) respectively Persistent hyperglycemia is an independent predictor of mortality [1]Tude Melo JR, et al. Neurosurgery 2010;67:1542-1547 [2] Melo JR, et al. Acta Neurochir 2010;152(9):1559-1565 [3] Seyed Saadat SM et al. Childs Nerv Syst 2012;28(10):1773-1777 Glucose control
  52. 52. Study Design Inclusion criteria (total n) Results Comments RL Smith et al [4] Retrospective review of a prospectively-collected Pediatric Neurotrauma Registry Children admitted with severe TBI as defined by GCS ≤ 8. Mean age 81 months (n=57) Mean glucose concentrations in the Late period (49-168 hours) was associated with unfavourable GOS at 6 months As part of the protocol, glucose administration was avoided for 48 hours after TBI A Cochran et al [5] Retrospective review Children admitted with a head regional Abbreviated Injury Score (AIS) ≥3 (n=170) Admission glucose had adjusted OR for head-injury related death of 1.01 (95% CI 1.003- 10.23) On multivariate analysis, GCS was also an independent predictor for head-injury related death [4] Smith RL, [4] Smith RL et al. Relationship Between Hyperglycemia and Outcome in Children with Severe Traumatic Brain Injury. Pediatr Crit Care Med 2012;13(1):85-91 [5] Cochran A, et al. Hyperglycemia and outcomes from pediatric traumatic brain injury. J Trauma. 2003;55(6):1035-1038 Glucose control
  53. 53. Study Design Inclusion criteria (total n) Results Comments Chong SL et al Retrospective review Children admitted with moderate and severe TBI as defined by GCS < 14. Mean age (n= 44) Univariate analysis – Hyperglycemia was a predictor for mortality, 14-day ventilation free days or 14-day PICU free days. But after stratifying to patients with GCS < 7, this was no longer statistically significant Initial hyperglycemia was associated with prolonged ICU stay, mechanical ventilation, and increased mortality
  54. 54. Does tight glucose control change outcomes? • A recent randomized trial among children admitted to the PICU (not specific to TBI): No significant difference in the number of days alive and free from mechanical ventilation at 30 days post randomization • The incidence of hypoglycemia being higher in the tight glucose control group compared to that with conventional glucose control • Macrae D, et al. A randomized trial of hyperglycemia control in pediatric intensive care. N Engl J Med 2014 Jan 9;370 (2):107-118
  55. 55. • It is currently 2 hours post injury. The temperature is 36.4oC What should you do now? A) Give cold saline – target a temperature of 30-32oC B) Surface cool – target 32-33oC C) Keep the current temperature
  56. 56. Temperature Control: Does cooling help? • Several small studies showed a positive effect of cooling on intracranial hypertension • Li H et al. Protective effect of moderate hypothermia on severe traumatic brain injury in children. J Neurotrauma 2009;26:1905-1909 • Biswas AK et al. Treatent of acute traumatic brain injury in children with moderate hyperthermia improves intracranial hypertension. Crit Care Med 2002;20:2742-2751 • Therapeutic hypothermia useful in newborn babies after hypoxic ischaemic encephalopathy • Shakaran S et al. Childhood Outcomes after Hypothermia for Neonatal Encephalopathy N Engl J Med. 2012 May 31; 366(22): 2085–2092. Cooling in TBI
  57. 57. Meta-analysis Ma CK et al. Is therapeutic hypothermia beneficial for pediatric patients with traumatic brain injury? A meta-analysis. Childs Nerv Syst 2013;29:979-984 Inclusion criteria: RCT, Pediatric TBI, hypothermia after TBI vs normothermia, and primary outcome Exclusion criteria: Non-RCT, TBI in adults, and no outcomes reported Cooling in TBI
  58. 58. Meta-analysis Ma CK et al. Is therapeutic hypothermia beneficial for pediatric patients with traumatic brain injury? A meta-analysis. Childs Nerv Syst 2013;29:979-984 Cooling in TBI
  59. 59. Meta-analysis Ma CK et al. Is therapeutic hypothermia beneficial for pediatric patients with traumatic brain injury? A meta-analysis. Childs Nerv Syst 2013;29:979-984 Cooling in TBI
  60. 60. Reference Study Description Data Quality and Reasons Results and Conclusion Hutchison et al 2008 Randomized controlled trial N = 225 Protocol: Randomized to cooling to 32-33 oC within 8 hours of injury for 24 hours, vs normothermia. Patients rewarmed at 0.5oC every hour Potential confounder was that marked hyperventilation (PaCO2 <30mmHg) was used as part of standard management in > 40% of patients and use of hypertonic saline was significantly reduced in the hypothermic groups vs normothermia group Unfavourable outcome at 6 months: 21% deaths in hypothermia group (vs 14% in normothermia group), more hypotension and more vasoactive agents in the hypothermia group during the rewarming period Hutchison JS et al. Hypothermia therapy after traumatic brain injury in children. N Engl J Med 2008;358:2447-2456 Cooling in TBI
  61. 61. Reference Study Description Data Quality and Reasons Results and Conclusion Adelson et al 2005 Randomized controlled trial N=75 Protocol: Cooled to 32- 33oC within 8 hours of injury for 48 hours, vs normothermia Outcome: Mortality, 3- and 6-month Glasgow Outcome Scale Unclear reporting of randomization methods, allocation concealment methods, and attrition Mortality 8% (Hypothermia) vs 16% (Normothermia) {p=0.44} No difference in 3- and 6-month Glasgow Outcome Scale. ICP was significantly reduced in initial 24 hours after TBI in hypothermia vs normothermia groups. Adelson PD et al. Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children. Neurosurgery 2005;56:740-754 Cooling in TBI
  62. 62. • Adelson et al. Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cook Kids): A phase 3, randomised controlled trial. Lancet Neurol 2013;12:546-53 • Children aged 0-17 were enrolled in the ED or ICU from 15 sites in USA, NZ and Australia, within 6 hours of injury, GCS 3-8 • Randomized, investigators who assessed outcomes were masked • Procedure for hypothermia group: • Rapidly cooled initially using iced saline (4oC) to 34-35oC, then surface cooled to 32-33oC. • Maintained for the requisite 48h period • Rewarming 0.5-1oC every 12-24 hours (slow rewarming) • Outcome measures assessed by intention to treat analysis: (Primary) mortality at 3 months (Secondary) GOS and GOS –E Peds at 3 months after injury Futility analysis was done after recruiting 77 patients and the trial was stopped – they detected no significant difference in mortality at 3 months, and no significant difference between the GOS or GOS-E Peds scores
  63. 63. Hutchison JS et al. Cooling of children with severe TBI. Lancet Neurol 2013;12:527-529
  64. 64. What about the effect of hypothermia on drugs in TBI? • PE Empey et al. Therapeutic Hypothermia Decreases Phenytoin Elimination in Children with Traumatic Brain Injury. Crit Care Med 2013;41:2379-2387 • Pharmacokinetic study – retrospectively evaluated 19 children who were randomized to 48 hours of cooling to 32-33oC • Therapeutic hypothermia significantly reduces phenytoin elimination in children with severe TBI leading to increased drug levels (and risk for toxicity) for an extended period of time after cooling Pharmacokinetic interactions between hypothermia and medications should be considered when caring for children receiving this therapy.
  65. 65. • It is currently 2 hours post injury. The temperature is 36.4oC What should you do now? A) Give cold saline – target a temperature of 30-32oC B) Surface cool – target 32-33oC C) Keep the current temperature
  66. 66. Objectives Which head-injured child requires a CT scan? Hyperosmolar agents Analgesics, Sedatives and Neuromuscular blockers Hyperventilation Prophylactic Anti-epileptics Glycemic Control Cooling heads in pediatric TBI
  67. 67. THANK YOU Chong.Shu-Ling@kkh.com.sg
  68. 68. Lyttle et al. Emerg Med J. Feb 2012 Age (yrs) Primary Outcome Secondary Outcome Inclusion Criteria Exclusion criteria CATCH < 17 Need for neurological intervention Brain injury on CT Blunt trauma resulting in LOC, amnesia, persistent vomiting (2 or more 15 mins apart), initial GCS 13 or more, injury within past 24 hrs Obvious penetrating injury or depressed fracture, focal neurological deficit, chronic GDD, HI due to NAI, return for reassesment of previous HI, pregnancy CHALICE < 16 Clinically significant ICI Presence of skull fracture Admission to hospital Any history or signs of injury to the head Refusal to consent PECARN < 18 Clinically important TBI - Present within 24hr of HI Trivial mechanism, penetrating trauma, known brain tumour, previous neurological disorder, prior neuroimaging, ventricular shunt, bleeding disorder, GCS < 14
  69. 69. ICP monitoring • 4 lines of evidence support the use of ICP monitoring in severe TBI 1. A frequently reported high incidence of intracranial hypertension in children with severe TBI 2. A widely reported association of intracranial hypertension and poor neurologic outcome 3. The concordance of protocol-based intracranial hypertension therapy and best-reported clinical outcomes 4. Improved outcomes associated with successful ICP-lowering therapies. • All Class III evidence • ICP monitoring of significant use in young children
  70. 70. Threshold for treatment of Intracranial Hypertension • Level III evidence – treatment may be considered at a threshold of 20mmHg • Taking reference from adult studies • While there are Class III studies that show sustained elevations in ICP (>20mmHg) are associated with poor outcomes in children after severe TBI, the absolute target for ICP-directed therapy has not been well established • Age-dependent values? • Need to define the relative value of ICP versus CPP-directed therapy in pediatric TBI
  71. 71. Phases of a clinical trial • Phase 0 – Pharmacodynamics and Pharmacokinetics • Phase 1 – Screening for safety • Phase 2 – Establishing the testing protocol • Phase 3 – Final Testing • Phase 4 – Postapproval studies

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